The repair of bone defects and augmentation of existing bone often require the use of permanent or bio-resorbable materials. Such materials may include autogenous bone graft, allogeneic graft, allogeneic bone graft, or alloplastic materials inclusive of various calcium phosphate ceramics, calcium phosphate cements, calcium sulfate materials, bioglass materials, and composites or other combinations thereof. Calcium sulfate, which is a form of plaster of paris, is a fully bioresorbable material which, for sometime, has been commonly used in cement and pellet form to repair bone defects.
When calcium sulfate is used as a cement to fill a bone void, fracture, or other defect, this material dissolves at a rapid rate, i.e., approximately one millimeter per week from the exterior of the cement towards the center thereof. Research of the present inventors has shown that this material causes precipitation of calcium phosphate deposits as it is resorbed at the surgical site. These precipitates, it has been shown, stimulate and direct the formation of new bone. On the other hand, it is important for purposes of optimal result that calcium sulfate, calcium phosphate, or any other bone repair material stay at the surgical site for a considerable period of time in order to inhibit soft tissue filling of the defect and to stimulate bone repair. However, currently used calcium sulfate materials are resorbed by human bone within two to seven weeks, depending upon the calcium sulfate form and the particular surgical site, which cannot be retained at the site for longer periods. As noted, such material is resorbed faster than it can be replaced by new bone thereby reducing its value to both patient and practitioner.
As such, the principal concern and difficulty expressed by practitioners (such as orthopedics or maxiofacial surgeons) are that calcium sulfate materials bio-resorb or dissolve too rapidly at a surgical or a recipient site, and, thereby, outpace the formation of new bone in human patients. Therefore, a need arises for improved calcium sulfate based compositions which can resorb at the recipient site in a rate desirably matching the rate bone growth.
On the other hand, poly(desaminotyrosyl-tyrosine alkyl ester carbonates, a family of tyrosine-derived polycarbonates, such as poly(desaminotyrosyl-tyrosine ethyl ester carbonates), poly(desaminotyrosyl-tyrosine butyl ester carbonates), poly(desaminotyrosyl-tyrosine hexyl ester carbonates), poly(desaminotyrosyl-tyrosine octyl ester carbonates), are a new class of degradable polymers developed for orthopedic applications. In various studies it has been reported that the above-referenced polymers are tissue compatible and they elicit direct bone apposition, particularly with poly(desaminotyrosyl-tyrosine ethyl ester carbonates). However, these bio-degradable polymers have not been used in combination with calcium sulfate for controlling resorption rate of calcium sulfate in vivo.